Caution advised in the use of CFTR modulator treatment for individuals harboring specific CFTR variants

In December 2020, the U.S. Food and Drug Administration (FDA) expanded the list of CFTR variants ap-proved for treatment with CFTR modulators drugs from 39 to 183. Clinicians should be aware that indi-viduals harboring certain variants approved for treatment may not respond to or benefit from this ther-apy. After review, the expert panel leading the CFTR2 project identified four categories of variants that may not result in a clinical response to modulator treatment: 15 variants assigned as non CF-causing; 45 variants of unknown significance; six variants known or suspected to cause mis-splicing as their primary defect rather than an amino acid substitution; and eight variants known to occur together in cis with another deleterious variant not expected to lead to CFTR protein (nonsense or frameshift). The potential risks and benefits of CFTR modulator therapy should be considered carefully for individuals harboring these variants.(c) 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Automated summary

In December 2020, the FDA expanded the list of CFTR variants approved for treatment from 39 to 183. However, clinicians should be aware that individuals with certain variants may not respond to or benefit from this therapy. Four categories of variants were identified as potentially not resulting in a clinical response to modulator treatment.